Reconstruction of thyroid follicles from isolated porcine follicle cells in three-dimensional collagen gel culture

Abstract

Thyroid follicles, an essential functional unit of the thyroid, are ball-like structures and exist in the extracellular matrix in vivo. Thus far, the follicles have not been reconstructed in any culture system. The presumed reason for that was that the in vitro environment for the follicle cells in monolayer culture markedly differed from their environment in vivo. We, therefore, considered that isolated follicle cells had to be localized in a three-dimensional environment of extracellular matrix, specifically collagen, to reconstruct thyroid follicles in vitro. At first, follicle cells were completely isolated. These cells were cultured in the three-dimensional collagen gel. An intracytoplasmic cavity first developed in individual cells. A single cell with the cavity then underwent cell division, and the follicle consisting of two cells was reconstructed. This gradually grew to be a large ball-like structure through proliferation of the component cells, and they exhibited morphological polarity specific for thyroid follicle cells. In addition, these cells clearly produced thyroid hormones. To the best of our knowledge, this report is the first instance of reconstruction of thyroid follicles in an in vitro culture system. This culture system is more useful than the monolayer culture system in that this system provides a more physiological environment for investigations of differentiation of follicle cells. Further experiments using this method will probably provide a new clue to the mechanism of thyroid folliculogenesis.